173676-59-0

Basic information

• Product Name: 4-Chloro-2-(trifluoroacetyl)aniline hydrochloride
• Synonyms: 4-CHLORO-2(1,1-DIHYDROXY-2,2,2-TRIFLUOROETHYL)ANILINE HCL;4-CHLORO-2,2,2-TRIFLUORO ACETYL ANILINE HYDROCHLORIDE;1-(2-aMino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride;Ethanone,1-(2-aMino-5-chlorophenyl)-2,2,2-trifluoro-, hydrochloride (1:1);Efavirenz Intermediate E-2;E2，173676-59-0;1-(2-Amino-5-chlorophenyl)-2,2,2-trifluoroethan-1-one hydrate hydrochloride;Efavirenz Intermediate: Trifluoroethanone
• CAS NO: 173676-59-0
• Molecular Formula: C₈H₅ClF₃NO*ClH
• Molecular Weight: 278.06
• EINECS: 1592732-453-0
• Product Categories: Amines and Anilines;Carbonyl Compounds;Aromatics Compounds;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 173676-59-0.mol

Chemical Properties

• Melting Point: 156-158°C
• Boiling Point: 282.3 °C at 760 mmHg
• Flash Point: 124.5 °C
• Appearance: /
• Vapor Pressure: 0.00339mmHg at 25°C
• Storage Temp.: Inert atmosphere,Room Temperature
• CAS DataBase Reference: 4-Chloro-2-(trifluoroacetyl)aniline hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Chloro-2-(trifluoroacetyl)aniline hydrochloride(173676-59-0)
• EPA Substance Registry System: 4-Chloro-2-(trifluoroacetyl)aniline hydrochloride(173676-59-0)

Safety Data

• Hazard Codes: Xi
• Hazardous Substances Data: 173676-59-0(Hazardous Substances Data)

Usage

Chemical Properties

Pale Yellow Solid

Uses

HIV reverse transcriptase inhibitor.

InChI:InChI=1/C8H5ClF3NO.ClH/c9-4-1-2-6(13)5(3-4)7(14)8(10,11)12;/h1-3H,13H2;1H

Synthetic route

ethyl trifluoroacetate, (383-63-1) + N-(2-bromo-4-chlorophenyl)pivalamide (195372-65-7) → 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0)

Conditions	Yield
Stage #1: N-(2-bromo-4-chlorophenyl)pivalamide With iodine; magnesium; lithium chloride In tetrahydrofuran at 20℃; for 6h; Stage #2: ethyl trifluoroacetate, In tetrahydrofuran at -15 - 20℃; for 0.5h; Stage #3: With hydrogenchloride; acetic acid at 75℃; for 4h; Reagent/catalyst; Temperature;	70%

N-(4-chloro-2-(2,2,2-trifluoroacetyl)phenyl)pivalamide (181190-33-0) → 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0)

Conditions	Yield
With hydrogenchloride In dimethoxyethane (DME) Heating / reflux;

4-chloro-aniline (106-47-8) → 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydroxide; water / toluene / 1 h / 15 - 40 °C 2.1: bromine; acetic acid / 1 h / 20 °C 3.1: magnesium; iodine; lithium chloride / tetrahydrofuran / 6 h / 20 °C 3.2: 0.5 h / -15 - 20 °C 3.3: 4 h / 75 °C View Scheme

1-(5-chloro-2-nitrophenyl)-2,2,2-trifluoroethanone → 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0)

Conditions	Yield
Stage #1: 1-(5-chloro-2-nitrophenyl)-2,2,2-trifluoroethanone With 5%-palladium/activated carbon; hydrogen In ethyl acetate at 20 - 60℃; under 750.075 - 10501.1 Torr; Stage #2: With hydrogenchloride for 30h;	121 g

1-bromo-3-chlorobenzene (108-37-2) → 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / -78 - -50 °C 1.2: -78 - 20 °C 2.1: sulfuric acid; nitric acid / dichloromethane / 2 h / 20 - 40 °C 3.1: hydrogen; 5%-palladium/activated carbon / ethyl acetate / 20 - 60 °C / 750.08 - 10501.1 Torr 3.2: 30 h View Scheme

1-(3-chlorophenyl)-2,2,2-trifluoroethanone (321-31-3) → 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sulfuric acid; nitric acid / dichloromethane / 2 h / 20 - 40 °C 2.1: hydrogen; 5%-palladium/activated carbon / ethyl acetate / 20 - 60 °C / 750.08 - 10501.1 Torr 2.2: 30 h View Scheme

3-iodochlorobenzene (625-99-0) → 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: isopropylmagnesium chloride / tert-butyl methyl ether / 1 h / -20 - -10 °C 1.2: -20 - 20 °C 2.1: sulfuric acid; nitric acid / dichloromethane / 2 h / 20 - 40 °C 3.1: hydrogen; 5%-palladium/activated carbon / ethyl acetate / 20 - 60 °C / 750.08 - 10501.1 Torr 3.2: 30 h View Scheme

1,3-Dichlorobenzene (541-73-1) → 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: magnesium; ethylene dibromide / tetrahydrofuran / 2 h / 40 - 50 °C 1.2: 0.5 h / 10 - 30 °C 2.1: sulfuric acid; nitric acid / dichloromethane / 2 h / 20 - 40 °C 3.1: hydrogen; 5%-palladium/activated carbon / ethyl acetate / 20 - 60 °C / 750.08 - 10501.1 Torr 3.2: 30 h View Scheme

1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0) → 1-(2-amino-5-chloro-phenyl)-2,2,2-trifluoro-ethanone (154598-53-5)

Conditions	Yield
With sodium hydrogencarbonate In water at 20℃; for 0.05h; Inert atmosphere; Schlenk technique;	99%
With sodium carbonate In dimethoxyethane (DME) pH=9;
With sodium hydrogencarbonate In water; toluene at 20℃; pH=7 - 8;

3-methoxybenzothiophene (10419-32-6) + 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0) → 2-chloro-11-trifluoromethyl[1]benzothieno[3,2-b]quinoline

Conditions	Yield
With indium(III) bromide In chlorobenzene at 110℃; under 760.051 Torr; for 24h; Inert atmosphere; Schlenk technique;	97%

1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0) + Cyclopropylacetylene (6746-94-7) → 2-cyclopropyl-4-(trifluoromethyl)-6-chloroquinoline

Conditions	Yield
With silver fluoride; triethylamine; triphenylphosphine In water at 120℃; Sealed tube;	85%

1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0) + hex-1-yne (693-02-7) → C14H13ClF3N (1456900-23-4)

Conditions	Yield
With silver fluoride; triethylamine; triphenylphosphine In water at 120℃; Sealed tube;	83%

1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0) + 4-n-methylphenylacetylene (766-97-2) → 6-chloro-2-(4-methylphenyl)-4-(trifluoromethyl)quinoline (1456900-24-5)

Conditions	Yield
With silver fluoride; triethylamine; triphenylphosphine In water at 120℃; Sealed tube;	80%

1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0) + phenylacetylene (536-74-3) → 2-phenyl-4-(trifluoromethyl)-6-chloroquinoline

Conditions	Yield
With silver fluoride; triethylamine; triphenylphosphine In water at 120℃; Reagent/catalyst; Sealed tube;	73%

1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0) → 2-chloro-11-trifluoromethyl-10H-quindoline

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydrogencarbonate / water / 0.05 h / 20 °C / Inert atmosphere; Schlenk technique 2: indium(III) bromide / 1,2-dichloro-benzene / 36 h / 170 °C / 760.05 Torr / Inert atmosphere; Schlenk technique View Scheme

1-(2-amino-5-chlorophenyl)-2,2,2-trifluoroethanone hydrochloride (173676-59-0) → 2-chloro-11-trifluoromethyl-5-methyl-10H-quindolinium 1,1,1-trifluoromethanesulfonate

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydrogencarbonate / water / 0.05 h / 20 °C / Inert atmosphere; Schlenk technique 2: indium(III) bromide / 1,2-dichloro-benzene / 36 h / 170 °C / 760.05 Torr / Inert atmosphere; Schlenk technique 3: toluene / 24 h / 50 °C / Inert atmosphere; Schlenk technique View Scheme

Upstream product

• 181190-33-0 N-(4-chloro-2-(2,2,2-trifluoroacetyl)phenyl)pivalamide 
• 383-63-1 ethyl trifluoroacetate, 
• 195372-65-7 N-(2-bromo-4-chlorophenyl)pivalamide 
• 106-47-8 4-chloro-aniline 
• 108-37-2 1-bromo-3-chlorobenzene 
• 321-31-3 1-(3-chlorophenyl)-2,2,2-trifluoroethanone 
• 625-99-0 3-iodochlorobenzene 
• 541-73-1 1,3-Dichlorobenzene 

Downstream Products

• 154598-53-5 1-(2-amino-5-chloro-phenyl)-2,2,2-trifluoro-ethanone 
• 391860-73-4 6-chloro-2-cyclopropyl-4-(trifluoromethyl)quinoline 
• 1456900-24-5 6-chloro-2-(4-methylphenyl)-4-(trifluoromethyl)quinoline 

Relevant articles and documents

Method for preparing 4-chloro-2-(trifluoroacetyl)aniline hydrochloride hydrate and free alkalis thereof

The invention discloses a method for preparing a 4-chloro-2-(trifluoroacetyl)aniline hydrochloride hydrate and free alkalis thereof. The method comprises the steps: (1) subjecting an intermediate, which is obtained through subjecting a compound with a structure represented by a formula IV shown in the description to a reaction, to a reaction with trifluoroacetate or a compound with a structure represented by a formula V or a formula VI shown in the description, and then, carrying out acid treatment, so as to obtain a compound with a structure represented by a formula I shown in the description; (2) subjecting the compound with the structure represented by the formula I to a nitration reaction under the catalysis of an acid, so as to obtain a compound with a structure represented by a formula II shown in the description; and (3) subjecting the compound with the structure represented by the formula II to nitro-to-amino reduction, thereby obtaining a compound with a structure represented by a formula III shown in the description.

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